A Functional Role for VEGFR1 Expressed in Peripheral Sensory Neurons in Cancer Pain

被引：111

作者：

Selvaraj, Deepitha ^{[1
]}

Gangadharan, Vijayan ^{[1
]}

Michalski, Christoph W. ^{[2
]}

Kurejova, Martina ^{[1
]}

Stoesser, Sebastian ^{[1
]}

Srivastava, Kshitij ^{[3
]}

Schweizerhof, Matthias ^{[1
]}

Waltenberger, Johannes ^{[4
,5
]}

Ferrara, Napoleone ^{[6
]}

Heppenstall, Paul ^{[7
,8
]}

Shibuya, Masabumi ^{[9
]}

Augustin, Hellmut G. ^{[3
,10
]}

Kuner, Rohini ^{[1
,8
]}

机构：

[1] Heidelberg Univ, Inst Pharmacol, D-69120 Heidelberg, Germany

[2] Heidelberg Univ, Dept Surg, D-69120 Heidelberg, Germany

[3] DKFZ ZMBH Alliance, German Canc Res Ctr, Div Vasc Oncol & Metastasis, D-69120 Heidelberg, Germany

[4] Univ Hosp Munster, Dept Cardiovasc Med, D-48149 Munster, Germany

[5] Univ Munster, Cells In Mot Cluster Excellence EXC CiM 1003, D-48149 Munster, Germany

[6] Univ Calif San Diego, La Jolla, CA 92093 USA

[7] European Mol Biol Lab, I-00015 Monterotondo, Italy

[8] Otto Meyerhof Ctr, Mol Med Partnership Unit, D-69120 Heidelberg, Germany

[9] Tokyo Dent & Med Univ, Grad Sch Med & Dent, Dept Mol Oncol, Bunkyo Ku, Tokyo 1138519, Japan

[10] Heidelberg Univ, Med Fac Mannheim CBTM, Dept Vasc Biol & Tumor Angiogenesis, D-68167 Mannheim, Germany

来源：

CANCER CELL | 2015年 / 27卷 / 06期

基金：

欧洲研究理事会;

关键词：

CELL LUNG-CANCER; MURINE MODEL; TUMOR; GROWTH; NERVE; ANGIOGENESIS; HYPERALGESIA; CHEMOTHERAPY; BEVACIZUMAB; MECHANISMS;

D O I：

10.1016/j.ccell.2015.04.017

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cancer pain is a debilitating disorder and a primary determinant of the poor quality of life. Here, we report a non-vascular role for ligands of the Vascular Endothelial Growth Factor (VEGF) family in cancer pain. Tumor-derived VEGF-A, PLGF-2, and VEGF-B augment pain sensitivity through selective activation of VEGF receptor 1 (VEGFR1) expressed in sensory neurons in human cancer and mouse models. Sensory-neuron-specific genetic deletion/silencing or local or systemic blockade of VEGFR1 prevented tumor-induced nerve remodeling and attenuated cancer pain in diverse mouse models in vivo. These findings identify a therapeutic potential for VEGFR1-modifying drugs in cancer pain and suggest a palliative effect for VEGF/VEGFR1-targeting anti-angiogenic tumor therapies.

引用

页码：780 / 796

页数：17

共 30 条

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